Viral interactions with the blood-brain barrier: old dog, new tricks

Abstract

Brain endothelial cells form a unique cellular structure known as the tight junction to regulate the exchanges between the blood and the parenchyma by limiting the paracellular diffusion of blood-borne substance. Together with the restricted pathway of transcytosis, the tight junction in the brain endothelial cells provides the central nervous system (CNS) with effective protection against both the foreign pathogens and the host immune cells, which is also termed the “blood-brain barrier.” The blood-brain barrier is particularly important for defending against neurotropic viral infections that have become a major source of diseases worldwide. Many neurotropic viruses are able to cross the BBB and infect the CNS through very poorly understood processes. This review focuses upon the structural and functional changes of the brain endothelial tight junction in response to viral infections in the CNS and how the tight junction changes may be studied with advanced imaging and recording approaches to reveal novel processes used by the viruses to cross the barrier system. Additional emphasis is placed upon new countermeasures that can act directly upon the tight junction to improve the pathogen clearance and minimize the inflammatory damage.

Keywords:

• blood brain barrier
• central nervous system
• claudin
• tight junction
• virus

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Additional information

Funding

This work is supported by grants from National Institute of Neurological Disorders and Stroke—R01NS052632 and P01NS059560; from National Institute of Diabetes and Digestive and Kidney Diseases - RO1DK084059; and from Department of Defense - HDTRA1-11-16-BRCWMD-BAA.